Lipids and Diabetic Retinopathy

Modjtahedi, Bobeck S.; Bose, Namrata; Papakostas, Thanos D.; Morse, Lawrence S.; Vavvas, Demetrios G.; Kishan, Amar U.

doi:10.3109/08820538.2015.1114869

Cited by 29 publications

(33 citation statements)

References 93 publications

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“…The early belief that dyslipidemia plays a critical role in DR, initiated several studies that examined the impact of lipid lowering drugs on DR. As discussed in the review by Modjtahedi et al[99] 2016, overall there are variable results but the majority of the studies support a protective role of some lipid lowering agents such as fenofibrate in mitigating hard exudates and DR. The beneficial effects of lipid lowering agents are not fully attributed to correcting dyslipidemia and may be attributed to anti-inflammatory, antioxidants and anti-apoptotic effects.…”

Section: Dyslipidemia and Development Of Drmentioning

confidence: 99%

“…The published literature suggested an association between diabetic dyslipidemia and DR; however, a more detailed and specific subtype of lipids or lipoproteins may have a clear pathogenic role rather than traditional lipid profile. In addition, alternative hypothesis suggests that initial damage to the retina barrier facilitate leakage of lipids and its oxidized metabolite to exert local adverse effects that are not necessarily mirrored by significant alteration in serum lipid profile[99]. …”

Section: Dyslipidemia and Development Of Drmentioning

confidence: 99%

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Obesity, metabolic syndrome and diabetic retinopathy: Beyond hyperglycemia

Mbata¹,

El-Magd²,

El-Remessy³

2017

WJD

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Diabetic retinopathy (DR) is the most feared ocular manifestation of diabetes. DR is characterized by progressive retinal damage that may eventually result in blindness. Clinically, this blindness is caused by progressive damage to the retinal microvasculature, which leads to ischemia, retinal swelling, and neovascularization. Retinopathy is associated with both type 1 and type 2 diabetes, with DR being the leading cause of new onset blindness in United States adults. Despite this strong association with diabetes, it must be noted that the development of retinopathy lesions is multifactorial and may occur in individuals without an established history of diabetes. Metabolic syndrome is a multifactorial condition of central obesity, hypertriglyceridemia, dyslipidemia, hypertension, fasting hyperglycemia, and insulin resistance. Although several studies examined the individual components observed in the metabolic syndrome in relation to the development of DR, there is conflicting data as to the association of the metabolic syndrome with the development of retinopathy lesions in non-diabetic subjects. This review will summarize the current literature on the evidence of the metabolic syndrome on retinopathy in subjects with and without an established history of diabetes. This review will also discuss some of the mechanisms through which metabolic syndrome can contribute to the development of retinopathy.

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Section: Dyslipidemia and Development Of Drmentioning

confidence: 99%

Section: Dyslipidemia and Development Of Drmentioning

confidence: 99%

Obesity, metabolic syndrome and diabetic retinopathy: Beyond hyperglycemia

Mbata¹,

El-Magd²,

El-Remessy³

2017

WJD

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“…Mirroring the pathophysiology in patients with type 2 diabetes, rodents fed a high fat diet (HFD) exhibit a slow onset of retinal complications, including retinal degeneration and impaired electroretinography (ERG) responses prior to the onset of microvascular disease (4–6). However, the mechanism underlying HFD-induced retinal dysfunction remains poorly understood (7,8). One potential mechanism whereby HFD contributes to retinal dysfunction is by promoting increased flux through the hexosamine biosynthetic pathway (HBP).…”

Section: Introductionmentioning

confidence: 99%

Consumption of a high fat diet promotes protein O-GlcNAcylation in mouse retina via NR4A1-dependent GFAT2 expression

Dai

Dierschke

Toro

et al. 2018

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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The incidence of type 2 diabetes, the most common cause of diabetic retinopathy (DR), is rapidly on the rise in developed countries due to overconsumption of calorie rich diets. Using an animal model of diet-induced obesity/pre-diabetes, we evaluated the impact of a diet high in saturated fat (HFD) on O-GlcNAcylation of retinal proteins, as dysregulated O-GlcNAcylation contributes to diabetic complications and evidence supports a role in DR. Protein O-GlcNAcylation was increased in the retina of mice fed a HFD as compared to littermates receiving control chow. Similarly, O-GlcNAcylation was elevated in retinal Müller cells in culture exposed to the saturated fatty acid palmitate or the ceramide analog Cer6. One potential mechanism responsible for elevated O-GlcNAcylation is increased flux through the hexosamine biosynthetic pathway (HBP). Indeed, inhibition of the pathway's rate-limiting enzyme glutamine-fructose-6-phosphate amidotransferase (GFAT) prevented Cer6-induced O-GlcNAcylation. Importantly, expression of the mRNA encoding GFAT2, but not GFAT1 was elevated in both the retina of mice fed a HFD and in retinal cells in culture exposed to palmitate or Cer6. Notably, expression of nuclear receptor subfamily 4 group A member 1 (NR4A1) was increased in the retina of mice fed a HFD and NR4A1 expression was sufficient to promote GFAT2 mRNA expression and O-GlcNAcylation in retinal cells in culture. Whereas palmitate or Cer6 addition to culture medium enhanced NR4A1 and GFAT2 expression, chemical inhibition of NR4A1 transactivation repressed Cer6-induced GFAT2 mRNA expression. Overall, the results support a model wherein HFD increases retinal protein O-GlcNAcylation by promoting NR4A1-dependent GFAT2 expression.

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“…It is also well known that inadequate glycemic control, hypertension, and dyslipidemia are risk factors for the development of macrovascular disease in diabetics. Although the importance of the first two factors in microcirculation have already been addressed by previous systematic reviews [12,13], the relationship between lipids and the development and severity of DR is complex and remains unclear [14]. …”

Section: Introductionmentioning

confidence: 99%

Statins and Fibrates for Diabetic Retinopathy: Protocol for a Systematic Review

Mozetic¹,

Freitas²,

Riera³

2017

JMIR Res Protoc

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BackgroundDiabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus, and more than 75% of patients who have had diabetes for more than 20 years will have some degree of DR. This disease is highly destructive to self-esteem and puts a high burden on public health and pension systems due to the effects that it has on people of working age. The current mainstay of treatment is laser photocoagulation, which causes impairment of vision and discomfort to patients. Thus, finding a systemic drug that could act on all microcirculation and prevent direct manipulation of the eyes would be highly desirable.ObjectiveTo assess the efficacy and safety of the drugs in the statin and/or fibrate groups for the prevention and treatment of DR.MethodsIn this systematic review, we will select randomized controlled trials of fibrates or statins used for the treatment or prevention of DR. Our search strategy will include free text terms and controlled vocabulary (eg, MeSH, Emtree) for, “diabetic retinopathy”, “statins”, “fibrates”, “hypolipidemic agents”, and for drugs from both groups. Databases that will be used include Medical Literature Analysis and Retrieval System/PubMed, Embase, Cochrane Central Register of Controlled Trials, Latin American and Caribbean Center on Health Sciences Information, Clinicaltrials.gov, World Health Organization International Clinical Trials Registry Platform, and OpenGrey, and we will not have language or date limits. Two review authors will independently select eligible studies and assess the risk of bias using the Cochrane Collaboration’s tool. We will report structured summaries of the included studies and, if possible, conduct meta-analyses.ResultsThis is a protocol for a systematic review, therefore results are not available. We registered a short version of this protocol before progressing in the review and we are currently in the process of selecting the studies for inclusion.ConclusionsIntensive glucose control and lowering blood pressure and lipids are mechanisms that protect macrocirculation in diabetic patients. Both macrovascular and microvascular events in diabetic patients appear to have a common pathway, starting with endothelial injury. Thus, prevention and treatment of microvascular events may benefit from the same interventions. In the review for which we have written this protocol, we will assess whether the use of lipid-lowering oral drugs of the statin and/or fibrate groups may prevent and/or retard progression of DR, with the added benefit of preserving visual acuity.Trial RegistrationPROSPERO CRD42016029746

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Lipids and Diabetic Retinopathy

Cited by 29 publications

References 93 publications

Obesity, metabolic syndrome and diabetic retinopathy: Beyond hyperglycemia

Obesity, metabolic syndrome and diabetic retinopathy: Beyond hyperglycemia

Consumption of a high fat diet promotes protein O-GlcNAcylation in mouse retina via NR4A1-dependent GFAT2 expression

Statins and Fibrates for Diabetic Retinopathy: Protocol for a Systematic Review

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